Subjects

Abstract

TAXOL1–4, a substance originally isolated from the Pacific yew tree (Taxus brevifolia) more than two decades ago, has recently been approved for the clinical treatment of cancer patients. Hailed as having provided one of the most significant advances in cancer therapy5, this molecule exerts its anticancer activity by inhibiting mitosis through enhancement of the polymerization of tubulin and consequent stabilization of microtubules6. The scarcity of taxol and the ecological impact of harvesting it have prompted extensive searches for alternative sources including semisynthesis, cellular culture production and chemical synthesis2,3. The latter has been attempted for almost two decades, but these attempts have been thwarted by the magnitude of the synthetic challenge. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Wani, M. C., Taylor, H. L., Wall, M. E., Coggon, P. & McPhail, A. T. J. Am. chem. Soc. 93, 2325–2327 (1971).

  2. 2

    Nicolaou, K. C., Dai, W.-M. & Guy, R. K Angew. Chem. int. Edn engl. 33, 15–44 (1994).

  3. 3

    Guenard, D., Gueritte-Voegelein, F. & Poitier, P. Acct Chem. Res. 26, 160–167 (1993).

  4. 4

    Rowinksy, E. K., Cazenave, L. A. & Donehower, R. C. J. natn. Cancer Inst. 82, 1247–1259 (1990).

  5. 5

    Paclitaxel (Taxol) Investigations Workshop Semin. Oncol. 20 (4, Suppl. 3), 1–60 (1993).

  6. 6

    Schiff, P. B., Fant, J. & Horwitz, S. B. Nature 277, 665–667 (1979).

  7. 7

    Nicolaou, K. C., Hwang, C.-K., Sorensen, E. J. & Claiborne, C. F. J. chem. Soc., chem. Commun. 1117–1118 (1992).

  8. 8

    Chamberlin, A. R. & Bloom, S. H. Org. React. 39, 1–83 (1990).

  9. 9

    McMurry, J. E. Chem. Rev. 89, 1513–1524 (1989).

  10. 10

    Nicolaou, K. C., Nantermet, P. G., Ueno, H. & Guy, R. K. J. chem. Soc., chem. Commun. 295–296 (1994).

  11. 11

    Ojima, I. et al. Tetrahedron 48, 6985–7012 (1992).

  12. 12

    Nicolaou, K. C., Liu, J. J., Hwang, C.-K., Dai, W.-M. & Guy, R. K. J. chem. Soc., chem. Commun. 1118–1120 (1992).

  13. 13

    Nicolaou, K. C., Yang, Z., Sorensen, E. J. & Nakada, M. J. chem. Soc., chem. Commun. 1024–1026 (1993).

  14. 14

    Griffith, W. P., Ley, S. V. Aldrichimica Acta. 23, 13–19 (1990).

  15. 15

    Sharpless, K. B. & Verhoeven, T. R. Aldrichimica Acta, 12, 63–74 (1979).

  16. 16

    Magee, T. V., Bornmann, W. G., Isaacs, R. C. A. & Danishefsky, S. J. J. org. Chem. 57, 3274–3276 (1992).

Download references

Author information

Affiliations

  1. Department of Chemistry, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California, 92037, USA

    • K. C. Nicolaou
    • , Z. Yang
    • , J. J. Liu
    • , H. Ueno
    • , P. G. Nantermet
    • , R. K. Guy
    • , C. F. Claiborne
    • , J. Renaud
    • , E. A. Couladouros
    • , K. Paulvannan
    •  & E. J. Sorensen
  2. Department of Chemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA

    • K. C. Nicolaou
    •  & E. J. Sorensen

Authors

  1. Search for K. C. Nicolaou in:

  2. Search for Z. Yang in:

  3. Search for J. J. Liu in:

  4. Search for H. Ueno in:

  5. Search for P. G. Nantermet in:

  6. Search for R. K. Guy in:

  7. Search for C. F. Claiborne in:

  8. Search for J. Renaud in:

  9. Search for E. A. Couladouros in:

  10. Search for K. Paulvannan in:

  11. Search for E. J. Sorensen in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/367630a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.